Introduction: Recently in elderly, homocysteine alone has been shown to be a better predictor of cardiovascular mortality than models based on classical risk factors. The pathophysiological pathway is however still unclear. Current view is that increased thrombogenicity, increased oxidative stress and over-activation of redox-sensitive inflammatory pathways, leads to impaired endothelial function.

Methods: Baseline data of the B-PROOF study are used to determine associations between homocysteine level and outcomes of vascular function. A subgroup was included (n=410, 58% male, age 72.6 ± 5.5 yrs, mean homocysteine level 15.2 ± 3.1 μmol/l). We assessed carotid intima media thickness (cIMT), carotid distensibility, using ultrasonograpy, and pulse wave velocity (PWV) and augmentation index (AIx), measured with applanation tonometry. Furthermore, office blood pressure measurements (n=410) and 24-hour blood ambulatory pressure recordings (n=70) were performed. Associations were tested using linear regression analysis and adjusted for age, gender, mean arterial pressure and heart rate.

Results:

The baseline analysis of the B-PROOF trial showed that log homocysteine was associated with PWV [β 0.010 (95%CI 0.006;0.014)] and with carotid IMT [β 0.0002 (95%CI 0.0001;0.0004)]. However, the association with IMT did not remain significant after adjustment for confounders [β 0.001 (95%CI −0.001;0.003)], but this finding remained for PWV [β 0.006 (95%CI 0.002;0.011)]. No significant association with homocysteine was found for AIx, distensibility or blood pressure levels.

Conclusions:

Homocysteine is possibly associated with arterial stiffness in elderly, measured with PWV. However, a subsequent question is whether lowering of homocysteine levels, indeed improves vascular function. Currently, this trial is still in progress.